Biology subjects

Prasad, A. A.

Publications and source records attributed to Prasad, A. A..

4 recordsLinked to original sources

bioRxiv2026

Multi-faceted role of dopamine afferents to the ventral pallidum in reward processing

The ventral pallidum (VP) is necessary for reward processing and a key node in dopamine (DA) pathways. Yet the direct DA inputs have not been studied during reward learning. Here, we elucidate the role of VP DA in reward processing using circuit tracing, fibre photometry, and behavioural pharmacology in male rats. We show that VP receives both non-DA and DA inputs from the midbrain. During an instrumental reward conditioning paradigm, we characterized VP DA activity using a DA sensor (GRAB_DA1h) across learning, extinction, re-acquisition, and motivational test. Followed by pharmacological manipulation using the DA-antagonist (fluphenazine) in VP to demonstrate a causal role in reward learning and motivation. Together our findings advance the functional contributions of non-canonical mesolimbic DA pathways.

animal behavior and cognition↗

bioRxiv2026

Subthalamic Nucleus dynamically encodes reward value and cognitive flexibility

The subthalamic nucleus (STN) is classically associated with motor control but is increasingly recognised as a key component of the neural circuits underlying cognition. However, how the STN encodes learned reward associations and updates these representations when environmental contingencies change remains unclear. Here, we combined fibre photometry calcium imaging and chemogenetic inhibition to identify the contribution of the STN in reward learning and cognitive flexibility. During established Pavlovian conditioning, calcium imaging of the STN showed distinctive responses to reward predictive cue and reward delivery, while no response was detected to unrewarded cues. Upon reversal of reward predictive cues, STN activity initially remained associated with the previously rewarded cue before remapping to the newly rewarded cue as animals acquired the updated contingency. Chemogenetic inhibition of the STN impaired cue discrimination on established Pavlovian conditioning, delayed reversal learning, and disrupted outcome-specific Pavlovian-to-instrumental transfer. Together these results demonstrate that STN activity is required for flexible updating of learned reward associations and goal-directed behaviour. These findings establish the STN as a dynamic integrative hub that encodes and updates learned reward representations to support cognitive flexibility, extending its role beyond motor control to include goal-directed behaviour. We show STN activity tracks reward-predictive cues and updates when contingencies reverse. Overall, these findings demonstrate that the STN is not just downstream of cortical control but actively supports updating of reward associations.

neuroscience↗

bioRxiv2020

The mesolimbic dopamine signatures of relapse to alcohol-seeking

The mesolimbic dopamine system comprises distinct compartments supporting different functions in learning and motivation. Less well understood is how complex addiction-related behaviors emerge from activity patterns across these compartments. Here we show how different forms of relapse to alcohol-seeking are assembled from activity across the ventral tegmental area and the nucleus accumbens. Using gCaMP and dLight fibre photometry, we show that self-administration and two forms of relapse (renewal/context-induced reinstatement and reacquisition) are associated with recruitment across the mesolimbic dopamine system. Using a variety of interventions, we show that this activity is causal to both forms of relapse. Finally, we use dissimilarity matrices to identify mesolimbic dopamine signatures of self-administration, extinction, and relapse. We show that signatures of relapse can be identified from heterogeneous activity profiles across the mesolimbic dopamine system and that these signatures differ for different forms of relapse.

neuroscience↗

bioRxiv2019

Complementary roles for ventral pallidum cell types and their projections in relapse

Ventral pallidum (VP) is a key node in the neural circuits controlling relapse to drug seeking but how this role relates to different VP cell types and their projections is poorly understood. Using male rats, we show how different forms of relapse to alcohol-seeking are assembled from VP cell types and their projections to lateral hypothalamus (LH) and ventral tegmental area (VTA). First, we used RNAScope in situ hybridization to characterize activity of different VP cell types during relapse to alcohol-seeking provoked by renewal (context-induced reinstatement). We found that VP Gad1 and parvalbumin (PV), but not vGlut2, neurons show relapse-associated changes in c-Fos expression. Next, we used retrograde tracing, chemogenetic, optogenetic, and electrophysiological approaches to study the roles of VPGad1 and VPPV neurons in relapse. We show that VPGad1 neurons contribute to contextual control over relapse (renewal), but not to relapse during reacquisition, via projections to LH where they converge with ventral striatal inputs onto LHGad1 neurons. This convergence of striatopallidal inputs at the level of individual LHGad1 neurons may be critical to balancing propensity for relapse versus abstinence. In contrast, VPPV neurons contribute to relapse during both renewal and reacquisition via projections to VTA but not LH. These findings show complementary roles for different VP cell types and their projections in relapse. VPGad1 neurons control relapse during renewal via projections to LH whereas VPPV neurons control relapse during both renewal and reacquisition via projections to VTA. Targeting these different pathways may provide tailored interventions for different forms of relapse.

neuroscience↗